Group A Streptococcus vaccine
Inventors
Pandey, Manisha • Batzloff, Michael • Good, Michael
Assignees
Publication Number
US-10301362-B2
Publication Date
2019-05-28
Expiration Date
2035-04-15
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Abstract
A method and composition for eliciting an immune response to group A streptococcal bacteria in a mammal is provided, which includes administering to the mammal an M protein fragment, variant or derivative thereof and a SpyCEP protein or peptide fragment, or an antibody to the SpyCEP protein or fragment to facilitate restoring or enhancing neutrophil activity. Also provided is an immunodominant peptide fragment of SpyCEP.
Core Innovation
The invention relates to a method and composition for eliciting an immune response to group A streptococcal (GAS) bacteria in a mammal by administering an M protein fragment, variant, or derivative thereof along with an agent that facilitates restoring or enhancing neutrophil activity. The agent may be a SpyCEP protein or peptide fragment or an antibody to the SpyCEP protein or fragment. This combination aims to enhance the immunological protection against GAS by restoring neutrophil function compromised by GAS virulence factors.
The problem solved by the invention arises from the difficulty in developing effective vaccines against GAS due to its virulence factors such as the M protein, which is anti-phagocytic, and particularly SpyCEP, a serine protease that cleaves and inactivates the neutrophil chemotactic agent interleukin-8, thus suppressing neutrophil activity. Neutrophils are essential for immunity induced by M protein-derived peptides like J8, but GAS strains, especially virulent CovR/S mutant strains, inhibit neutrophil recruitment through SpyCEP activity, reducing vaccine efficacy. The invention addresses this by combining M protein fragments with agents, such as SpyCEP peptides or antibodies, that restore or enhance neutrophil activity, thereby improving protective immunity.
Claims Coverage
The patent includes five inventive features disclosed in independent claims related to compositions and methods for eliciting an immune response to group A Streptococcus in mammals.
Composition comprising J8 peptide and SpyCEP peptide
A composition suitable for administration to a mammal comprising an isolated J8 peptide of SEQ ID NO:58 or a J8 peptide variant having at least 90% amino acid sequence identity to SEQ ID NO:58, together with an isolated SpyCEP peptide of SEQ ID NO:18 or a SpyCEP variant peptide having at least 90% amino acid sequence identity to SEQ ID NO:18.
Composition with specific J8 peptide variants and SpyCEP peptide
A composition suitable for administration to a mammal comprising an isolated J8 peptide variant selected from SEQ ID NO:59, 60, 61, or 62 and an isolated SpyCEP peptide of SEQ ID NO:18 that facilitates restoring or enhancing neutrophil activity.
Method of eliciting immune response via composition administration
A method of eliciting an immune response to group A Streptococcus in a mammal comprising administering an effective amount of the claimed compositions to the mammal, specifically compositions comprising J8 peptides and SpyCEP peptides or variants thereof.
The claims collectively cover compositions comprising J8 peptides and SpyCEP peptides or their variants designed to restore neutrophil function and methods of using these compositions to elicit immune responses to group A Streptococcus in mammals, thereby addressing bacterial immune evasion mechanisms and enhancing vaccine efficacy.
Stated Advantages
Combining J8 peptide and SpyCEP peptides elicits synergistic enhanced protection against virulent GAS strains compared to either component alone.
Anti-SpyCEP antibodies can neutralize SpyCEP's IL-8 degrading activity, thereby restoring neutrophil chemotactic function and improving immune response.
Use of an immunodominant SpyCEP peptide epitope (SEQ ID NO:18) for vaccine formulation improves safety by avoiding the use of the whole recombinant SpyCEP protein.
Developed J8 peptide variants induce high titers of antibodies specifically recognizing streptococcal sequences, potentially improving vaccine specificity and efficacy.
Documented Applications
Prevention and treatment of infectious diseases caused by group A streptococcal bacteria in mammals, including humans.
Vaccination against group A streptococcal diseases such as rheumatic fever, rheumatic heart disease, impetigo, pharyngitis, necrotizing fasciitis, and other serious infections caused by GAS.
Therapeutic administration of anti-SpyCEP antibodies to enhance neutrophil activity and treat existing GAS infections.
Use of compositions including M protein fragments and SpyCEP peptides or antibodies for immunizing mammals against GAS infections, including those caused by antibiotic-resistant and virulent CovR/S mutant strains.
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